The major areas of research interest is to build a comprehensive program of research on the serology of HPV natural infection and HPV vaccination. These studies utilize the biobank of specimens from the various studies on HPV in DCEG such as the Costa Rica HPV16/18 Vaccine trial. We will examine the immunological determinants of protection recently reported for the HPV-16/18 vaccine against infection with other, phylogenetically related HPV types. Since protection against heterologous HPV types is partial, vaccine failures for these HPV types are expected in the early years following vaccination. We will also perform a nested case-control study within CVT that will evaluate key immunological markers among vaccinated women who develop infections with the types for which partial protection has been observed (failures), and will compare them to those observed among a group of controls who did not develop these infections after vaccination (successes). This effort is expected to be a multiyear project that will require initial validation and evaluation of novel immunological markers that can subsequently be applied in the nested case-control study.